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168 effect of antiglucocorticoids on dexamethasone-induceo inhibition of urioine incorporation and cell lysis in isolated mouse thymocytes
56s
166
HORMONAL CONTROL OF CELL PROLIFERATION ANTECEDENT EPITHELIUM P.J.M. Tutton
and D.H. Barkla,
Monash
IN COLONIC
CARCINOMAS
AND IN THEIR
University,
Melbourne,
Australia
Cognizance of hormonal factors regulating cell division in tumours of the breast, prostate and uterus has led to dramatic improvement in both the quality and the duration of life in those patients whose tumours are not suitable for potentially curative surgery. However, scientific literature contains only sparse reports concerning possible hormonal influences on other tumours. This report concerns the effects of biogenic amines, prostaqlandins, steroids and cyclic nucleotides on the crypt epithelium of the normal colon and on primary, experimentally-induced colonic tumours and on xenoqrafted human colorectal tumours. Cell proliferation in the crypt epithelium of the large intestine was stimulated by autonomic nerves acting via alphap adrenoceptors. By contrast, cell proliferation in tumours of the large intestine was stimulated by histamine and/or serotonin. In each of the tissues examined beta-adrenerqic agonists temporarily suppress cell division. Glucocorticoid hormones, oestrogens and androqens stimulated cell division in tumours of the large intestine, whereas analoques of prostaglandin El, E2 and Fza were each found to inhibit both rat and human tumours. In each of the tissues assessed, derivatives of cyclic AMP inhibited cell division and derivatives of cyclic GMP promoted cell division.
167
EFFECT OF GASTROINTESTINAL HORMONES ON THE GROWTH OF GASTROINTESTINAL TUMOR CELLS IN VITRO. M.T.Vuillot, O.Kobori & F.Martin, Groupe de Recherche sur les Cancers Digestifs, INSEPM U-252, FacultC de Medecine, 21033 Dijon (France).
We have studied the effect of a variety of hormones on the growth in vitro of 2 rat digestive tumor cell lines: line BV-9 established from a gastric carcinoma induced by methylnitronitrosoguanidine and line KlZ/TR established from a colon carcinoma induced by dimethylhydrasine. Both lines were cultivated for 2 days in serum-free medium supplemented or not with various hormones. Non digestives hormones (thyroxine, epinephrine, hydrocortisone,oestradiol,progesterone, testosterone) did not enhance the growth of BV-9 cells. Insulin , blocked pentaqastrin and hormonally-inactive peptides related to gastrin were also without effect on BV-9 and K12/TR cells. On the other hand, tetragastrin and glucagon significantly enhanced the growth of both lines (from cancer 128% to 408%). Glucagon was able to stimulate the growth of gastrointestinal cells cultivated in optimal concentration of tetraqastrin, suggesting the existence of different receptors for the 2 hormones. These results establish the hormonal dependence of gastrointestinal tumors in vitro, but the in vivo significance has yet to be demonstrated.
168
EFFECT OF ANTIGLUCOCORTICOIDS ON DEXAMETHASONE-INDUCED RATION AND CELL LYSIS IN ISOLATED MOUSE THYMOCYTES U7 INSERM, 0. Duval, S. Durant & F. Homo-Delarche. Necker, 161 rue de Sevres, 75015 Paris, France
INHIBITION Dept
OF URIDINE
INCORPO-
of Pharmacology,
Hopital
We have compared in isolated mouse thymocytes the action of progesterone, of DXH a 17D-carboxamide derivative of dexamethasone and of RU-38486 (l), on dexamethasoneinduced inhibition of uridine incorporation and cell lysis, with the. affinities of these molecules for glucocorticoid receptors. All of these molecules did not exert any sign'ficant influence on the parameters tested except at concentrations higher than lo- 6M, but are able to counteract the actions of dexamethasone. In addition, there was a striking relationship between the affinity of a giv n compound for glucofrom corticoid receptor, as estimated by its ability to displace ( 3 H)-dexamethasone actions. RU-38486, specific binding sites, and its capacity to block dexamethasone which was a very potent competitor of dexamethasone binding, the inhibitory action as well as the lytic action of 5 x 10 l-3 fold excess basis and therefore represents a useful antiglucocorticoid compound. (1) Philibert D, Deraedt R & Teutsch Tokyo 1981, Abstract 1463, p. 668.
G.
8th International
Congress
of Pharmacology,
166
HORMONAL CONTROL OF CELL PROLIFERATION ANTECEDENT EPITHELIUM P.J.M. Tutton
and D.H. Barkla,
Monash
IN COLONIC
CARCINOMAS
AND IN THEIR
University,
Melbourne,
Australia
Cognizance of hormonal factors regulating cell division in tumours of the breast, prostate and uterus has led to dramatic improvement in both the quality and the duration of life in those patients whose tumours are not suitable for potentially curative surgery. However, scientific literature contains only sparse reports concerning possible hormonal influences on other tumours. This report concerns the effects of biogenic amines, prostaqlandins, steroids and cyclic nucleotides on the crypt epithelium of the normal colon and on primary, experimentally-induced colonic tumours and on xenoqrafted human colorectal tumours. Cell proliferation in the crypt epithelium of the large intestine was stimulated by autonomic nerves acting via alphap adrenoceptors. By contrast, cell proliferation in tumours of the large intestine was stimulated by histamine and/or serotonin. In each of the tissues examined beta-adrenerqic agonists temporarily suppress cell division. Glucocorticoid hormones, oestrogens and androqens stimulated cell division in tumours of the large intestine, whereas analoques of prostaglandin El, E2 and Fza were each found to inhibit both rat and human tumours. In each of the tissues assessed, derivatives of cyclic AMP inhibited cell division and derivatives of cyclic GMP promoted cell division.
167
EFFECT OF GASTROINTESTINAL HORMONES ON THE GROWTH OF GASTROINTESTINAL TUMOR CELLS IN VITRO. M.T.Vuillot, O.Kobori & F.Martin, Groupe de Recherche sur les Cancers Digestifs, INSEPM U-252, FacultC de Medecine, 21033 Dijon (France).
We have studied the effect of a variety of hormones on the growth in vitro of 2 rat digestive tumor cell lines: line BV-9 established from a gastric carcinoma induced by methylnitronitrosoguanidine and line KlZ/TR established from a colon carcinoma induced by dimethylhydrasine. Both lines were cultivated for 2 days in serum-free medium supplemented or not with various hormones. Non digestives hormones (thyroxine, epinephrine, hydrocortisone,oestradiol,progesterone, testosterone) did not enhance the growth of BV-9 cells. Insulin , blocked pentaqastrin and hormonally-inactive peptides related to gastrin were also without effect on BV-9 and K12/TR cells. On the other hand, tetragastrin and glucagon significantly enhanced the growth of both lines (from cancer 128% to 408%). Glucagon was able to stimulate the growth of gastrointestinal cells cultivated in optimal concentration of tetraqastrin, suggesting the existence of different receptors for the 2 hormones. These results establish the hormonal dependence of gastrointestinal tumors in vitro, but the in vivo significance has yet to be demonstrated.
168
EFFECT OF ANTIGLUCOCORTICOIDS ON DEXAMETHASONE-INDUCED RATION AND CELL LYSIS IN ISOLATED MOUSE THYMOCYTES U7 INSERM, 0. Duval, S. Durant & F. Homo-Delarche. Necker, 161 rue de Sevres, 75015 Paris, France
INHIBITION Dept
OF URIDINE
INCORPO-
of Pharmacology,
Hopital
We have compared in isolated mouse thymocytes the action of progesterone, of DXH a 17D-carboxamide derivative of dexamethasone and of RU-38486 (l), on dexamethasoneinduced inhibition of uridine incorporation and cell lysis, with the. affinities of these molecules for glucocorticoid receptors. All of these molecules did not exert any sign'ficant influence on the parameters tested except at concentrations higher than lo- 6M, but are able to counteract the actions of dexamethasone. In addition, there was a striking relationship between the affinity of a giv n compound for glucofrom corticoid receptor, as estimated by its ability to displace ( 3 H)-dexamethasone actions. RU-38486, specific binding sites, and its capacity to block dexamethasone which was a very potent competitor of dexamethasone binding, the inhibitory action as well as the lytic action of 5 x 10 l-3 fold excess basis and therefore represents a useful antiglucocorticoid compound. (1) Philibert D, Deraedt R & Teutsch Tokyo 1981, Abstract 1463, p. 668.
G.
8th International
Congress
of Pharmacology,